Discover Dialogue: Chemist George Whitesides

What is intelligence? Where does life come from? Those are the big questions

George Whitesides, 64, is the Mallinckrodt Professor of Chemistry at Harvard University. He is a Renaissance thinker whose ideas crisscross scientific disciplines and an outspoken critic who is fond of reminding scientists that they really understand very little. He believes that science is rapidly changing from separate studies of biology, chemistry, and physics to a new discipline that combines all three. Although he tries to confine his research to basic science, he holds many patents and has spun off companies, including several working on soft lithography, a method for building nanostuff.

Do you have a word for what you do?

W: I don’t have a word for it. We apply physical science to biology, we apply physics to materials science, we think about chemical principles in microfluidic devices. We are working in three or four areas. There is nanotech, where the thrust is to develop methods that enable people to make small structures easily. Then there are emergence, complexity, and self-assembly, the notion of complex systems putting themselves together and developing characteristic behaviors. This area of complexity is to me one of the big areas of science, whether the subject is the power breakdown on the East Coast or how a reactor works. The last area is tools for analyzing the cell, understanding how to control it.

So you’re a tinkerer?

W: Tinkerer is a funny word because it has in some sense an Edisonian quality, and an ideal project for our group is something in which we start with a question that’s fundamental science, such as: Where does lightning come from? And we try to understand it, and then find out how to apply it, and then build a prototype, and then do research engineering, and 10 years later there’s a start-up.

How did a chemist become an inventor?

W: Part of it is curiosity. Part of it is talking to all sorts of people, trying to consult in various areas. The chemistry is typically only a very small part.

The disciplines—biology, chemistry, physics—seem to be coalescing.

W: It is all beginning to come together. One issue at the university is that you have to have a set of courses that add up to a coherent whole. But the courses are taught along one set of axes, and research is being done along a completely different set of axes now. It is an interesting disconnect, and a big problem. What do I teach? I teach a general course on molecular biology for anyone who wants to know about molecular biology. At the end of the course you have a pretty good idea what’s going on. And then I teach another, more specialized course for chemists.

The place where this kind of education really goes on is with graduate students because when they eventually get jobs, it is in chemistry departments, and bioengineering departments, and chemical engineering departments, and biology departments—all over the map.

Some of them go to biotech companies . . .

W: Yes, although many students are not attracted to big companies these days. If you are in electronics you may still have to go to the big companies because the best possible talent is still in electronics and telecommunications. But in biotechnology there are still many interesting opportunities in start-ups.

Who is helping you?

W: The business of the lab is doing first experiments. And that requires a big group with a lot of skills, imaginative people. The graduate students are mostly chemists and materials scientists, with a few biologists; the postdoctoral students are everything—they’re electrical engineers, and chemical engineers, and physicists, and biologists, and M.D.-Ph.D.s.

Is a lot of time spent sitting around and chewing over things?

W: Particularly at the beginning of projects. Once something is started and the experiments are working, then that becomes, in a proper sense, more normal science, where one can proceed according to principles that are well understood. But the business of figuring out where to get a foothold in a new area can get pretty difficult. It requires a fair amount of intuition. It’s one place where someone older can make a contribution. I’ve seen a lot of projects start and fail and succeed and so on and so forth. Often you have some helpful instinct to bring to the story.

What do you mean by “complexity”?

W: Take the weather, or take air traffic control, or take electric power grids. They are complex systems with components that interact with one another. Things happen in these systems that we really, really do not understand.

Can you describe an example of a complexity experiment?

W: This is more of a physics experiment than biology: Take a polystyrene dish and put a bunch of little steel balls into it, then put a magnet underneath. The balls kind of follow the poles of the magnet around and roll around on the inside of the dish in a circle. Then they do something that to me is really quite amazing: That disorganized cloud resolves itself into a series of concentric rings of balls, all of them following one another. The individual balls also resolve themselves into a very highly ordered pattern, so they are equally spaced in each ring, and the rings are equally spaced relative to one another. The whole system spontaneously organizes itself in a very complicated way. Then after about 10 minutes the whole thing suddenly freezes onto the surface. How does that happen?

I find it immensely interesting because what’s going on there relates to such problems as where lightning comes from. Turns out we don’t know. What if you shuffle your feet across the carpet and there’s a spark? Where does that come from? We don’t know really where that comes from either. The world is just full of neat stuff that we don’t know the origins of.

Are you trying to come up with some basic physical explanations for where things come from?

W: When you look at systems that self-organize into complex behaviors and understand what the rules are, the bigger question becomes whether there are situations in which your understanding of the individual cases can help you predict the behavior of the complex system. Are there layers of complexity that are not predictable? This turns out to be a very important in biology. The genomics guys will tell you that by understanding the gene you understand the cell. Then there are people—I happen to be one of them—who say that the gene is interesting but probably largely irrelevant to much of what goes on in the cell. So what strategy do you use to understand a system that is as complicated as an organism? Do you look at behavior and try to understand that, or do you really follow science’s historically honored reductionist approach and pick it apart from the bottom and then rebuild it from there? Science has tended to do both, but for the last 30 to 40 years in biology there has been a great enthusiasm for reductionism.

So you’re using the really small to predict the really large?

W: Yes. I’m not sure that in my lifetime we will make these connections across all scales, but recently we have been working with things that are small. The nice thing about small things is that it enables you to look for new phenomena, and it enables you to put a lot of information into a small area. In a practical sense you can make a laboratory on a chip kind of thing.

Will we ever be able to understand these systems?

W: The question is: If you have a system with enough moving parts, can you really predict all of its behaviors? Is there something that these systems share in common that would form a new kind of science, or is it all idiosyncratic and special? And I don’t know the answer to that right now.

What about extraordinarily complex questions, such as the origin of life?

W: This notion of life as a traceable continuum with increasing complexity is something that I think is going to be pretty troubling to work out.

With so little understood, it doesn’t sound like this is the end of science, as science writer John Horgan proposed in his landmark book.

W: It should have been called The End of Physics. I mean, the big questions to me are: What is intelligence? Where does life come from? What is self-awareness? These are questions that are at least as interesting as questions like: Why do things fall down? Those who are Horgan physicists will tell you that there can’t be anything fundamentally new, that it’s all built into the Schrödinger equation. But the fact of the matter is that’s not a useful statement because the Schrödinger equation is terrific for the hydrogen atom and pretty much useless for everything else. It has no predictive value. I don’t think that any amount of information I have on the laws of attraction between atoms is going to tell me why someone plays the piano particularly well.

Why is a simple cell so fascinating to you?

W: What can be more interesting than life? What is a cell? What is an animal? Life in a certain sense is a sack of chemical reactions. That’s one way to look at it. Another is to say that it’s an entity that is compartmentalized, energy dissipating, adaptive, and self-replicating. A third way of looking at it is to say it’s a network of catalytic reactions, and amazingly, it replicates itself. But I haven’t said anything yet. I’ve just given names to things I don’t understand.

What do we understand?

W: We understand a lot about chemistry and physics, and some about biology. But even here there is a lot we don’t understand intuitively. You know, chemistry has been around for a while, and we all know about covalent bonds. Except it turns out that we don’t really understand covalent bonds at all. Can I predict the bond energy of H20? The answer is: exactly. And the computer that has predicted this took a series of integrals that I understand conceptually, which contain all sorts of different terms—nuclear repulsion, delocalization, this and that; it’s taken all of that and come up with the right answer. But I actually don’t understand it. And that’s the simplest molecule. What about a cell?

Then how can you hope to comprehend it?

W: We’re going to start to try to make things that have primitive, lifelike characteristics. If you can make something that replicates itself and has some of these lifelike characteristics, then perhaps one is moving in the right direction. And I think we do understand in principle many things about how a cell works. But in practice, we don’t.

Are we making any progress with the promise of nanotechnology?

W: There is evolutionary nanotechnology. There are people at places like Texas Instruments and Intel doing clever engineering to make things smaller and smaller. They have working microprocessors with “wires” that are only 90 nanometers across.

What about the more revolutionary stuff?

W: Interestingly, the area where there has been the most activity and the most progress has been in the interface between chemistry and materials science. There are many new kinds of materials. There are quantum dots for fluorescence and color, and buckyballs for electrical conductivity. There’s an absolute explosion of people making structures that are very, very small.

Why is it all taking so long?

W: I sense a little impatience in some people about the progression of nanotechnology, but if you take biotechnology, we didn’t have just one or two things that did the job. It wasn’t just the double helix, it was the double helix and the polymerase chain reaction and cloning, and on and on. Many different technologies have to be on the shelf for an area of technology to explode with applications.

You have suggested a kind of periodic table for clusters of atoms that might be used as basic building materials.

W: Yes, maybe these structures—clusters of atoms—form a sort of a periodic table of their own, and there are a series of elements that are clusters of atoms rather than being individual atoms because you can begin to make matter in new ways out of them. Why would you want to do that? The answer is, we don’t know right now. But there is a wonderful opportunity for discovery. I’m willing to predict with great confidence that over the course of 20 years this is going to produce stuff that’s very useful.

Are you also studying tiny structures in biology to get nano ideas from nature?

W: Yes. When one thinks about what’s discussed in nanotechnology, it is little motors and little batteries and things like that—those are already in cells. But they don’t exist at all in the way that futurists have thought about them, as devices with little motors and propellers. Bacteria use tails—flagella—which are a lot different from propellers. So one of the most interesting parts of the science in this area is to look at the biology from the vantage of an engineer, to say: Here’s a rotary motor, here’s how batteries operate in that world. How can I mimic those ideas outside a cell?

Do you worry about any of this going wrong? Did you read Michael Crichton’s book Prey, about nanotech machines running amok?

W: The difficulty with ideas like Prey is that they tend to ignore some very basic notions, like the logic of size. You’ve got to have these nano devices powered, and they have to have a certain size to talk to one another. It is not an accident that bacteria are one micron by three microns, not nanometers. It takes about that much space, even at a molecular level, to store the information in the machinery to make them do the things that they do. It’s also not an accident that they eat glucose—they need power.

What about futurist Bill Joy’s warning: that self-replicating nanodevices could proliferate and consume the planet, turning it into a gray goo?

W: As far as I can see, it’s complete nonsense. If there were new kinds of self-replicators, there might be a problem. But there are not. The level of hard science in these ideas is really very low.